A Phase 1 Clinical Trial of Anti-CD19 Chimeric Antigen Receptor T Cells for Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma
This study will assess safety and feasibility of infusing genetically modified autologous T cells transduced to express a chimeric antigen receptor targeting the B cell surface antigen Cluster of Differentiation 19 (CD19).
• Dose expansion Cohorts:
• Cohort B (Burkitt):
• Participants must have a diagnosis of relapsed or refractory Burkitt Lymphoma
‣ Participants with Burkitt lymphoma must have relapsed or failed to respond to at least 1 prior line of multiagent chemoimmunotherapy with prior exposure to both an anti-CD20 antibody agent and an anthracycline.
⁃ No significant circulating disease, defined as an elevated total lymphocyte count above the upper limit of normal (ULN) due to the presence of malignant cells.
• Participants must have measurable disease as defined below:
‣ Participants with Burkitt Lymphoma must have Positron Emission Tomography (PET)-positive disease according to Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification
• Cohort M/W (Marginal/Waldenström):
• Participants must have a diagnosis of relapsed or refractory Marginal Zone Lymphoma (MZL), or Lymphoplasmacytic Lymphoma (LPL)/Waldenström Macroglobulinemia (WM):
• o Participants with indolent lymphomas (nodal or extranodal marginal zone lymphoma, and lymphoplasmacytic lymphoma) must have relapsed after or have been refractory to ≥ 2 prior lines of multi-agent chemoimmunotherapy including prior exposure to an anti-CD20 antibody and an alkylating agent.
• Participants must have measurable disease as defined below:
• o Participants with Marginal Zone Lymphoma or Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia: must either have PET-positive disease according to Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification or serum monoclonal immunoglobulin M (IgM) paraprotein \> 0.5 g/dL.
• Participants with indolent lymphoma (Marginal Zone Lymphoma or Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia) must have symptomatic disease necessitating systemic treatment.
• In addition, all participants must meet the following criteria:
• CD19-positive by either immunohistochemistry or flow cytometry analysis on any biopsy. If prior anti-CD19 therapy has been administered, CD19-positivity has to be re-established on the most recent biopsy.
• Age ≥18 years at the time of consent.
• Absolute lymphocyte count \> 100/UL.
• Eastern Cooperative Oncology Group (ECOG) performance status \< 2.
• Adequate organ function, defined as:
∙ Adequate bone marrow function for apheresis and lymphodepleting chemotherapy
‣ Hemoglobin \>8 gm/dl (transfusions allowed)
‣ Platelets \>50,000/uL (transfusions allowed)
‣ Absolute Neutrophil Count (ANC) \> 500/uL
‣ alanine aminotransferase (ALT)/aspartate aminotransferase (AST) \< 3 x institutional upper limit of normal (ULN) and Total bilirubin \< 1.5 mg/dl x institutional ULN, except with Gilbert's syndrome
‣ Serum Creatinine \< 2 x the institutional ULN
‣ Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) \> 40% as assessed by echocardiogram or multiple uptake gated acquisition (MUGA) within 3 months of screening. Repeat testing may occur at Investigator's discretion.
• Adequate vascular access for leukapheresis procedure (either peripheral line or surgically placed line).
• Women of childbearing potential (defined as all women physiologically capable of becoming pregnant) must have a negative serum or urine pregnancy test AND agree to use highly effective methods of contraception for 1 year after the last dose of anti-CD19 CAR-T cells.
• Males who have partners of childbearing potential must agree to use an effective barrier contraceptive method.
• Ability to understand a written informed consent document, and the willingness to sign it.